Muscle precursor cells (MPC) are essential for muscle growth and regeneration. Sca-1 has been proposed to negatively regulate growth and differentiation of MPC. Preliminary data suggest that Sca-1 is regulated by the NFAT family of transcription factors. The goal of this proposal is to further investigate and define the role of NFAT in Sca-1 regulation. The role of specific NFAT isoforms in Sca-1 activation will be examined using cells lacking or overexpressing NFAT proteins expressed in muscle (NFATc1-c3). To determine if NFAT directly activates Sca-1 expression, the ability of NFAT to bind the Sca-1 promoter will be investigated; the regions of the Sca-1 promoter necessary and sufficient for regulation by NFAT will also be determined. Activation of Sca-1 expression by growth factors involved in muscle growth and repair will be studied, and dependence on NFAT determined. These studies may result in the development of new methods for manipulating myogenic stem cells in disease, regeneration, and aging, as well as define new therapeutic targets for enhancing muscle growth.